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Anaphylaxis in the Clinic
Pediatric Grand Rounds
Justin Jones, DO
Resident ETSU Pediatrics
PL--3
PL
Case

Chief Complaint:


12-year
12year--old boy is brought to the clinic after being
stung by a bee.
History of Present Illness:

He had been well until he was stung on his right
forearm, while playing in the yard. He initially
complained of localized pain and swelling. Fifteen
minutes later, he began to complain of shortness of
breath. His parents observed him to be wheezing. He
also said that he felt very weak and dizzy. His parents
brought him immediately to the clinic.
Case Continued

Exam








VS: T 37.1, P 120, R 39, BP 69/45.
General: Mild respiratory distress. Drowsy and pale,
but awakens to voice.
Skin: Generalized urticaria. Face moderately pale.
HEENT: No conjunctival edema. Lips and tongue are
not swollen. Voice sounds normal.
Heart: Tachycardic without murmurs.
Lung: Mild wheezing and fair aeration with minimal
retractions.
Abdomen: Soft and non
non--tender.
Extremities: The bee sting site on his right forearm is
unremarkable with no foreign body seen.
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Case Continued

Assessment:



Early anaphylactic shock






Assess ABC’s
O
Oxygen
IM epinephrine
Activate 911 for transfer to nearest ER facility
Albuterol
IV is started with fluid bolus of normal saline
Diphenhydramine IV, Cimetidine IV,
Methylprednisolone IV
Emergent Recognition in the Clinic
Anaphylaxis is highly likely when any one of the
following are present:

Acute onset of an illness within minutes to several
hours.


Definition

Plan:


Anaphylaxis
Skin, mucosal tissue, or both are involved. (eg, generalized
hives pruritus or flushing,
hives,
flushing swollen lips-tongue-uvula)
lips tongue uvula)
Respiratory compromise

Can include dyspnea, wheeze–bronchospasm, stridor,
reduced peak expiratory flow (PEF), hypoxemia

Persistent gastrointestinal symptoms

Reduced blood pressure (BP) or associated
symptoms of end organ dysfunction


Acute onset life threatening reaction that
affects at least two body systems and often
the whole body.
y
Emergent Recognition in the Clinic

Reduced BP after exposure to known
allergen for that patient

Infants and children: low systolic BP (age
(agespecific) or greater than 30% decrease in
systolic BP
crampy abdominal pain, vomiting
hypotonia [collapse], syncope, incontinence
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Pathophysiology




Increased secretion from mucous membranes
Increased bronchial smooth muscle tone
Decreased vascular smooth muscle tone
Increased capillary permeability occur after
exposure to an inciting substance.

Pathophysiology

Classic form



Anaphylactoid reaction

These effects are produced by the release of
mediators, which include histamine, leukotriene C4,
prostaglandin D2, and tryptase.



Epidemiology







True incidence is unknown.
Fatal anaphylaxis is relatively rare; milder forms occur much more
frequently.
Up to 500
500--1,000 fatal cases of anaphylaxis per year are estimated to
occur in the United States.
Lifetime prevalence of anaphylaxis is estimated at 11-2% of the
population as a whole
whole, no racial differences are known
known.
Cultural and socioeconomic differences may influence exposure
rates.
Overall, women have a higher incidence of anaphylaxis than
men, but, in some series of children, males predominate.
Children most commonly affected by peanut allergy.
Mediator release occurs when the antigen binds to antigenantigenspecific immunoglobulin E attached to previously sensitized
basophils and mast cells.
The mediators are released almost immediately when the
antigen binds.
Exposure to an inciting substance causes direct release of
mediators, a process that is not mediated by IgE.
Increased mucous secretion and increased bronchial smooth
muscle tone, as well as airway edema, contribute to the
respiratory symptoms observed in anaphylaxis.
Cardiovascular effects result from decreased vascular tone and
capillary leakage.
Histamine release in skin causes urticarial skin lesions
Morbidity/Mortality

Approximately 1 in 5000 exposures to a parenteral dose
of a penicillin or cephalosporin antibiotic causes
anaphylaxis.

More than 100 deaths per year are reported in the United States.

Fewer than 100 fatal reactions to Hymenoptera stings
are reported each year in the United States

One to 2% of people receiving IV radiocontrast
experience some sort of reaction.


The majority of these reactions are minor, and fatalities are rare.
Low molecular weight contrast causes fewer and less severe
reactions.
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Risk Factors

Atopy

History

Prevalence of atopy is approximately 3737-53%
in patients with anaphylaxis
Asthma
 Food Allergy
 Early Childhood

Almost always involve the skin or mucous
membranes.


The upper respiratory tract commonly is
involved, with complaints of nasal congestion,
sneezing, or coryza.

History
Eyes may itch and tearing may be noted.
Conjunctival injection may occur.
 Dyspnea is present when patients have
bronchospasm or upper airway edema
edema.
More than 90% of patients have some combination of
urticaria, erythema, pruritus, or angioedema.
Cough, hoarseness, or a sensation of tightness in the
throat may indicate significant airway obstruction.
History

Hypoxia and hypotension may cause
weakness, dizziness, or syncope.
 Chest pain may occur due to bronchospasm
or myocardial ischemia (secondary to
hypotension and hypoxia).




GI symptoms of cramplike abdominal pain with
nausea, vomiting, or diarrhea also occur but are
less common, except in the case of food allergy.
The clinician may not realize that
that, while
reactions are usually rapid in onset, they also
may be delayed.
For reasons that are not well understood, a lack
of dermal findings is more common in children
than in adults.
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Physical


General: VS can be normal or abnormal with
hypotension, tachypnea, tachycardia. May also
have anxiety, tremor, or sensation of cold
Skin: Urticaria



L i
Lesions
are red
d and
d raised,
i d and
d th
they sometimes
ti
h
have
central blanching.
Cutaneous exposure (eg, insect bite). The involved
area is erythematous, edematous, and pruritic.
Angioedema usually is nonpruritic and associated
lesions are nonpitting. Lesions most often appear on
the lips, palms, soles, and genitalia.
Physical

Pulmonary: Upper airway compromise may occur and
stridor may be noted. Can have hoarseness, quiet voice,
may lose speaking ability.



Cardiovascular: Cardiovascular examination is normal in
mild cases.



Mechanisms

Drugs and foods are the most common causes.



Peanuts, tree nuts, and shellfish are the most commonly
implicated foods.
Antibiotics (especially penicillins) and nonsteroidal antiantiinflammatory drugs are the most common drugs.
Foreign protein is often the inciting agent.
agent




On initial exposure, the antigen elicits generation of an IgE
antibody.
The antibody residue binds to mast cells and basophils.
On reexposure, the antigen binds to the antibody, and the
receptors are activated.
Clinical manifestations result from release of immune response
mediators such as histamine, leukotrienes, tryptase, and
prostaglandins.
Complete airway obstruction is the most common cause of death
in anaphylaxis.
Wheezing is common when patients have lower airway
compromise
i d
due tto b
bronchospasm
h
or mucosall edema.
d
In more severe cases, compensatory tachycardia occurs due to
loss of vascular tone.
Intravascular volume depletion may take place as a
consequence of capillary leakage.
Relative bradycardia has been reported.
Mechanisms
Parenteral exposures tend to result in
faster and more severe reactions. Most
severe reactions occur soon after
exposure.
exposure
 The faster a reaction develops, the more
severe it is likely to be.


While most reactions occur within hours,
symptoms may not occur for as long as 33-4
days after exposure.
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Drugs

Penicillin and cephalosporin antibiotics are the most
commonly reported medical agents in anaphylaxis.




Drugs

Because of their molecular and immunologic similarity, crosscrosssensitivity may exist.
Reports based on skin testing indicate that about 10% of
patients allergic to a penicillin antibiotic are allergic to
cephalosporins.
Reactions to medications tend to be more severe and
rapid in onset when the antibiotic is administered
parenterally.
A drug reaction may occur in a patient with no prior
history of drug exposure.

Hymenoptera Stings

Hymenoptera stings are a common cause of allergic reaction and
anaphylaxis.


Food Allergy


Local reaction and urticaria without other manifestations of
anaphylaxis are much more common than fullfull-blown anaphylaxis.


In the United States, Hymenoptera envenomations result in fewer than
100 reported deaths per year.
Generalized urticaria is a risk factor for subsequent
q
anaphylaxis;
p y
; but a
local reaction, even if severe, is not a risk factor for anaphylaxis.
Caution patients treated and released from the ED or clinic after an
episode of anaphylaxis or generalized urticaria from Hymenoptera
envenomation to avoid future exposure when possible.


Consider referral to an allergist for desensitization, particularly when
further exposure is likely.
Consider prescribing a treatment kit with an epinephrine auto
auto--injector
and oral antihistamine. Both are effective measures in preventing or
ameliorating future reactions.
Aspirin and NSAIDs commonly are implicated in
anaphylaxis. Bronchospasm is common in
patients with reactive airway disease and nasal
polyps. Cross
Cross--reactivity often occurs between
the various NSAIDs.
ACE inhibitors, widely used in the treatment of
hypertension, are associated with angioedema
in 0.50.5-1.0% of patients who take them. Systemic
anaphylaxis is rarely associated with these
agents.



Symptoms usually are mild and limited to the GI tract,
but fullfull-blown anaphylaxis can occur.
Fatalities are rare compared to number of exposures;
however, the number of exposures is so high that foods
may be the most common cause of anaphylaxis.
Anaphylaxis due to foods may be an under recognized
cause of sudden death and an unappreciated cause of
diagnosed anaphylaxis.
Commonly implicated foods include peanuts, tree nuts,
legumes, fish and shellfish, milk, and eggs.
Reports of severe allergic reactions to peanuts are
increasing.
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Environmental Allergies



Latex allergy is an increasingly recognized
problem in medical settings, where use of gloves
and other latex products is ubiquitous.
Most reactions are cutaneous or involve the
mucous membranes
membranes.
Anaphylactic reactions occur and have been
reported with seemingly benign procedures
For example:

Foley catheter insertion, intraperitoneal exposure to
gloves during surgery.

Exercise Induced

Intravenous Radiocontrast Media
Exercise--induced syndrome
Exercise
Prior food ingestion followed by vigorous
exercise
 Aspirin/NSAID use prior to exhertion
 Premonitory fatigue, pruritis, flushing, diffuse
warmth, erythema, urticaria
 Urticaria: 11-2 cms in size unlike cholinergic
urticaria
 Progression to angioedema, GI colic,
laryngeal edema

IV administered radiocontrast media causes an anaphylactoid reaction that
is clinically similar to true anaphylaxis and is treated in the same way. The
reaction is not related to prior exposure.



Shellfish or "iodine allergy" is not a contraindication to use of IV contrast and
does not mandate a pretreatment regimen.
The term iodine allergy is a misnomer. Iodine is an essential trace element
present throughout the body. No one is allergic to iodine. Approximately 11-3% of
patients who receive hyperosmolar IV contrast experience a reaction.
Use of LMW contrast decreases incidence of reactions to approximately 0.5%.

Reactions to radiocontrast usually are mild most commonly urticarial

Mucosal exposure either GI or GU to radiocontrast agents has not been
reported to cause anaphylaxis

Pretreatment with antihistamines or corticosteroids and use of LMW agents
lead to lower rates of anaphylactoid reactions to IV contrast.


Risk of a fatal reaction has been estimated at 0.9 cases per 100,000 exposures.
A history of prior reaction is not a contraindication to GI or GU use of these
agents.
Catamenial
Rare disorder Reaction to progesterone in the luteal phase of the menstrual cycle resulting in anaphylaxis
Pathogenesis is still poorly understood
C b lif h
Can be life threatening
i
Progesterone challenge is diagnostic
Treatment consists of H1‐ H2‐ receptor blockers, glucocorticoids and LHRH agonists Definitive therapy is hysterectomy with bilateral oophorectomy
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Differential Diagnosis
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Angioedema
Myocardial Infarction
Anxiety
Pulmonary Embolism
Asthma
Toxicity, Scombroid
Conversion Disorder
Urticaria
Epiglottitis
Tracheal Foreign Bodies
Globus hystericus
Hereditary angioedema
Monosodium glutamate poisoning
Masquraders






Scombroid fish poisoning
 Tryptase normal
Mastocytosis
 ‐tryptase elevated
Vasovagal syndrome
 Bradycardia, tryptase normal
C1 esterase deficiency and C1 esterase deficiency and angioedema
 Hypocomplementemia
 Low C1 esterase inhibitor
Flush syndromes
 Carcinoid syndrome
Non‐‐organic syndromes
Non
 Munchausen stridor
 Vocal cord dysfunction
 Globus hystericus
Dangers of anaphylaxis





Symptoms
% Child
% Adults
--------------------------------------------------------------------------Cutaneous
94
100
Respiratory
88
69
Cardiovascular
21
41
Gastrointestinal
22
24



Tryptase levels normal
No urticaria
No hypotension
Workup

When typical symptoms are noted in association with a likely exposure, diagnosis is virtually
certain.

The only potentially useful test at the time of reaction is measurement of serum mast cell tryptase.

Tryptase levels may aid in later diagnosis and treatment.

Histamine: Peaks 5
5--30 minutes










Ancillary testing may help assess severity of reaction, although this is primarily a clinical judgment. When
unclear, ancillary testing may help establish the diagnosis.
Tryptase is released from mast cells in both anaphylactic and anaphylactoid reactions. Levels are usually
raised in severe reactions. Mast cell tryptase is raised transiently with blood levels reaching a peak
approximately an hour after reaction onset.
Consider the test in cases for which diagnosis of anaphylaxis is uncertain.
The utility of this test awaits full evaluation.
Sample drawn within 1 hour
Plasma or serum frozen immediately
Elevated in scombroid poisoning
24--hour histamine or N
24
N--methylhistamine helpful
Cardiac monitoring in patients with severe reactions and in those with underlying cardiovascular
disease is important, particularly when adrenergic agonists are used in treatment.
Pulse oximetry also is useful.
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Desensitization Regimens
Sensitivity Testing

Testing for sensitivity to penicillin antibiotics may be useful when a penicillin
or cephalosporin antibiotic is the drug of choice for a serious infection in a
patient who has a history of severe allergic reaction.





Obtain informed consent, and ensure that resuscitative equipment is immediately
available.
Protocols for acute testing for allergy to penicillin or cephalosporin antibiotics
involve administration of increasing IV doses of the chosen antibiotic, while
observing the patient for pruritus, flushing, urticaria, dyspnea, hypotension, or
other manifestations of anaphylaxis
anaphylaxis.
If no manifestations are observed, a full dose of the antibiotic may be
administered safely.
A suggested protocol for IV testing begins with 0.001 mg of the chosen
drug. At 1010-min intervals, incrementally increase the dose while observing
the patient.
Many other protocols exist. In most circumstances, perform desensitization
on an inpatient basis. If the necessary resources are available,
desensitization may be performed in the ED.






Treatment





First line is to assess Airway, Breathing, and
Circulation
Patient should be removed from stimulus as
soon as possible
Evaluation of skin, orientation, and weight of
patient should be approximated
Patient should be given oxygen especially if
stridor or wheezing is present
Epinephrine 0.01 mg/kg of 1:1000 solution with
a maximum of 0.3 mls

Injection given intramuscularly in anterolateral thigh
Desensitization regimens for penicillin and cephalosporin antibiotic
allergy have been shown effective.
Because these regimens are lengthy (approximately 6 h), they have
limited applicability to the clinic.
When patients wait for long periods in the ED or in an observation unit,
consider desensitization regimens.
A typical desensitization regimen involves administering the
antibiotic of choice in an initial dose of 0.01 mg. While observing the
patient, double the dose every 1010-15 minutes until a full dose has
been administered.
Desensitization regimens do not protect against nonnon-IgE
IgE--mediated
reactions that may be severe or even life threatening like StevensStevensJohnson syndrome.
While theoretically attractive, premedication regimens have not been
clinically shown to decrease incidence or severity of IgE
IgE--mediated
allergic reactions to antibiotics.
Treatment Cont.





Epinephrine can be repeated if no clinical
improvement in 5 minutes.
Albuterol can be used in cases with respiratory
distress and wheezing
g
If hypotension a problem, administer IV fluids.
Patient can also be placed in supine or
Trendelenburg.
When in the clinic call 911 for immediate
transport to emergency department.
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Further Care

b2-agonist

H1-antihistamine

H2-antihistamine

Diphenhydramine/Benadryl
St id
Steroids

Glucagon








Methylprednisolone
Intropic, chronotropic, and vasoactive effects that are independent of
beta-receptors.
Endogenous catecholamine release
Vasopressors
Possible intubation
Treatment success operationally may be defined as complete resolution of
symptoms followed by a short period of observation. The purpose of
observation is to monitor for recurrence of symptoms that can occur in
biphasic anaphylaxis
Hospital admission is required for patients who

Cimetidine/Tagamet



Albuterol


Care




Consider ICU admission for patients with persistent hypotension.
Inpatient management of airway compromise consists of continuation of
parenteral and inhaled adrenergic agents and corticosteroids
Cutaneous manifestations of anaphylaxis are treated with repeated doses of
antihistamines.
Treatment outside clinic



Patients who have been successfully treated for
anaphylaxis usually should continue
antihistamines for 22-5 days to prevent
recurrence.
When corticosteroids have been used as p
part of
the initial treatment, common practice continues
that treatment for a short period.
Patients should be given EpiEpi-Pen or Epi
Epi--Pen Jr.
Auto--Injector: This product is an auto
Auto
auto--injecting
syringe containing 0.3 mL 1:1000 epinephrine
solution, 0.3 mg (Epi
(Epi--Pen) or 0.3 mL 1:2000
solution, 0.15 mg (Epi(Epi-Pen Jr).
(1) fail to respond fully
(2) have a recurrent reaction or a secondary complication
(3) experience a significant injury from syncope
(4) need intubation.
(5)As with many other conditions, consider a lower admission threshold when
patients are at age extremes or when they have significant comorbid illness.
Prevention

Caution patients who are discharged after an episode of
anaphylaxis to avoid exposure to an inciting agent.




When no inciting agent has been identified, consider referral to
an allergist to identify the cause of anaphylaxis.
Inform patients who react to Hymenoptera venom of the
availability of desensitization therapy,
therapy and consider a
self--administered epinephrine prescription.
self
On discharge, warn patients of the possibility of recurrent
symptoms, and instruct them to seek further care if this
occurs.
Children are likely to outgrow most food allergies except
shrimp and peanuts.
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3/9/2010
Prevention

References
Sting avoidance is important for hypersensitive
persons. Patients must be educated concerning
steps they can take to reduce the risk of insect
stings.

Caution patients to avoid use of perfumes or hygiene
products
d t th
thatt iinclude
l d perfumes,
f
particularly
ti l l flflorall
scents, as these attract flying Hymenoptera.
Brightly colored clothing attracts bees and other
pollinating insects.
Avoid locations of known hives or nests, and avoid
using equipment that disturbs the hive.
Persons who are sensitive to Hymenoptera and who
must be outdoors should carry a sting kit.








Clark S, Camargo CA. 2008. Epidemiology of Anaphylaxis. Immunol
Allergy Clin N Am. 27 (2007) 145–163.
E-Medicine Anaphylaxis. Accessed January 2010.
Guha Krishnaswamy, M.D., Presentation Anaphylaxis: Food, Drug, Venoms, and Latex.
Kuwaye TT, MD, MS. Chapter V.2. Anaphylaxis and Other Acute Allergic
Reactions. Case Based Pediatrics For Medical Students and Residents.
November 2002.
http://www.hawaii.edu/medicine/pediatrics/pedtext/s05c02.html
Estelle F, Simons R. 2010. Anaphylaxis. Journal of Allergy and
Clinical Immunology. 125:2. Supplement 2. S161-S181.
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